• Korean Journal of Biological Psychiatry
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• v.15 no.3
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• pp.175-185
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• 2008

Accumulating evidence has suggested the existence of reciprocal communication between immune, endocrine, and neurotransmitter system. Cytokine hypothesis of depression implies that increased pro-inflammatory cytokine such as -1, IL-6, IL-12, TNF-${\alpha}$, and IFN-${\gamma}$ in major depression, acting neuromodulators, play a key role in the mediation of behavioral, neuroendocrine, and neurochemical disturbances in depression. Concerning the relation between cytokines and serotonin metabolism, pro-inflammatory cytokines have profound effects on the metabolism of brain serotonin through the enzyme indoleamine-2,3-dioxygenase(IDO) that metabolizes tryptophan, the precursor of 5-HT to neurodegenerative quinolinate and neuroprotective kynurenate. The neurodegeneration process is reinforced by the neurotoxic effect of the hypercortisolemia during depression. From this perspective, it is possible that efficacy of antidepressants in the treatment of depression may, at least in part, rely on downregulation of pro-inflammatory cytokine synthesis. So, the use of cytokine synthesis inhibitors or cytokine antagonists may be a new treatment approach in depression. However, at present the question whether cytokines play a causal role in the onset of depression or are mere epiphenomena sustaining depressive symptoms remains to be elucidated. Nevertheless, cytokine hypothesis has created new perspectives in the study of psychological and pathophysiological mechanism that are associated with major depression, as well as the prospect for developing a new generation antidepressants.

• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.78-86
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• 2005

Dioxins, especially 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin), are ubiquitous environmental contaminants. TCDD is known that it has toxic effects in animals and humans, including chloracne, immune, reproductive and developmental toxicities, carcinogenicity, wasting syndrome and death. TCDD induces a broad spectrum of biological responses, including disruption of normal hormone signaling pathways, reproductive and developmental defects, immunotoxicity, liver damage, wasting syndrome and cancer. Many researches showed that TCDD induces gene expression of transcriptional factors related cell proliferation, signal transduction, immune system and cell cycle arrest at molecular and cellular levels. These toxic actions of TCDD are usually mediated with AhR (receptor, resulted from cell culture, animal and clinical studies). cDNA microarray can be used as a highly sensitive and informative marker for toxicity. Additionally, microarray analysis of dioxin-toxicity is able to provide an opportunity for the development of candidate bridging biomarkers of dioxin-toxicity. Through microarray technology, it is possible to understand the therapeutic effects of agonists within the context of toxic effects, classify new chemicals as to their complete effects on biological systems, and identify environmental factors that may influence safety.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.252-260
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• 2019

Background: Increases in the average global temperature cause heat stress-induced disorders by disrupting homeostasis. Excessive heat stress triggers an imbalance in the immune system; thus protection against heat stress is important to maintain immune homeostasis. Korean ginseng (Panax ginseng Meyer) has been used as a herbal medicine and displays beneficial biological properties. Methods: We investigated the protective effects of Korean ginseng extracts (KGEs) against heat stress in a rat model. Following acclimatization for 1 week, rats were housed at room temperature for 2 weeks and then exposed to heat stress ($40^{\circ}C$/2 h/day) for 4 weeks. Rats were treated with three KGEs from the beginning of the second week to the end of the experiment. Results: Heat stress dramatically increased secretion of inflammatory factors, and this was significantly reduced in the KGE-treated groups. Levels of inflammatory factors such as heat shock protein 70, interleukin 6, inducible nitric oxide synthase, and tumor necrosis factor-alpha were increased in the spleen and muscle upon heat stress. KGEs inhibited these increases by down-regulating heat shock protein 70 and the associated nuclear $factor-{\kappa}B$ and mitogen-activated protein kinase signaling pathways. Consequently, KGEs suppressed activation of T-cells and B-cells. Conclusion: KGEs suppress the immune response upon heat stress and decrease the production of inflammatory cytokines in muscle and spleen. We suggest that KGEs protect against heat stress by inhibiting inflammation and maintaining immune homeostasis.

• IMMUNE NETWORK
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• v.10 no.2
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• pp.46-54
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• 2010

Background: Graft-versus-host disease (GVHD) is initiated when alloreactive donor T cells are primed by host APCs to undergo clonal expansion and maturation. Since there is a controversy regarding the role of nonhematopoietic cells in GVHD, we wanted to investigate the influence of MHC disparity on nonhematopoietic cells on the pathogenesis of GVHD in the MHC-haplomismatched C57BL/6 ($H-2^b$) or DBA/2 $(H-2^b){\rightarrow}$unirradiated ($C57BL/6{\times}DBA/2$) $F_1(BDF_1;\;H-2^{b/d})$ murine model of acute GVHD (aGVHD) or chronic GVHD (cGVHD). Methods: We generated ($BDF_1{\rightarrow}C57BL/6$), ($BDF_1{\rightarrow}DBA/2$), and ($BDF1{\rightarrow}BDF_1$) chimeras and examined GVHD-related parameters and donor cell engraftment in those chimeras. Results: Using this experimental system, we found that 1) severe aGVHD across MHC Ag barrier depends on the expression of nonhematopoietically rather than hematopoietically derived alloAgs for maximal GVHD manifestations; 2) host APCs were sufficient to break B cell tolerance to self molecules in cGVHD, whereas host APCs were insufficient to induce autoimmunity in aGVHD; 3) donor cell engraftment was greatly enhanced in the host with MHC-matched nonhematopoietic cells. Conclusion: Taken together, our results provide an insight into how MHC disparity on GVHD target organs contribute to the pathogenesis of GVHD.

• Food Science and Biotechnology
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• v.17 no.1
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• pp.95-101
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• 2008

Some biological activities of Beauveria bassiana were studied to elucidate pharmacological function of B. bassiana-infected larva of the silkworm. The mycelium consisted mainly of carbohydrate (65.8%), followed by protein (15.9%) and fat (8.3%). Glucose (68.8%), mannose (7.1%), and galactose (6.1%) were major components in carbohydrates. Ten amino acids including glutamine, threonine, valine, aspartic acid, alanine, leucine, serine, glycine, arginine, and isoleucine were found in protein as major amino acids. Various extracts were prepared from the freeze-dried mycelium of B. bassiana by systemic extraction and their biological activities were investigated. Among tested fractions, the hot-water extract (HW) contributed significantly to the anti-coagulant activity, anti-complementary activity, and stimulation of intestinal immune system. The methanol extract (ME) increased acetylcholinesterase (AChE) inhibition activity and reactive oxygen species (ROS) scavenging activity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2935-2941
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• 2012

Biological response modifiers (BRMs) can alter interactions between the immune system and cancer cells to boost, direct, or restore the body's ability to fight disease. Mice with ethylnitrosourea- (ENU) induced leukemia were here used to monitor the therapeutic efficacy of lipopolysaccaride (LPS), Bacillus Calmette Guerin (BCG) and sheep erythrocytes (SRBC). Flow cytometry based CD34+ positivity analysis, clonogenicity, proliferation and ultrastructure studies using scanning electron microscopy (SEM) of stem cells in ENU induced animals with and without BRMs treatment were performed. BRMs improved the stem-stromal relationship structurally and functionally and might have potential for use as an adjunct in human stem cell therapy.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.211-217
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• 2021

The treatments of nervous system diseases (NSDs) have long been difficult issues for researchers because of their complexity of pathogenesis. With the advent of aging society, searching for effective treatments of NSDs has become a hot topic. Ginseng polysaccharides (GP), as the main biologically active substance in ginseng, has various biological properties in immune-regulation, anti-oxidant, anti-inflammation and etc. Considering the association between the effects of GP and the pathogenesis of neurological disorders, many related experiments have been conducted in recent years. In this paper, we reviewed previous studies about the effects and mechanisms of GP on diseases related to nervous system. We found GP play an ameliorative role on NSDs through the regulation of immune system, inflammatory response, oxidative damage and signaling pathway. Structure-activity relationship was also discussed and summarized. In addition, we provided new insights into GP as promising neuroprotective agent for its further development and utilization.

• Korean Journal of Veterinary Research
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• v.34 no.2
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• pp.307-313
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• 1994

We have previously shown that crude water extract of Euonymus alatus (EA) had strong prophylactic effect against chemically induced-and tumor cell implanted-cancer, and that the mechanisms responsible for its antitumor effects were due to nonspecific enhancement of the NK cell activities and the cell mediated immunity. However, it was unknown that any components of crude extract did work so, since it consisted of several components. In this paper, we fractionated the crude watar EA-extract into several fraction such as hexane-, ethylether-, ethyl acetate-, n-butanol- and water soluble-fraction, and screened the immune regulating activities of each fraction by the evaluation of lymphokine production and activated lymphocyte proliferation. As a result of the component fraction of EA-extract, it was found that n-butanol fraction was a potent immunostimulator, and the remained water soluble fraction also contained some stimulator, But, other fraction did not showed any remarkable effect. It is therefore suggested that EA-glycosides in n-butanol fraction may be new one of the potent biological response modifiers. The present study was also undertaken in an efforts to investigate the effects of elm-bark(EB, Ulmus clavidiana var japonica), which has been used for curing ulcer and inflammation as a folk medicine without any kind of experimental evidence to support this, on the cellular- and humoral-immune responses, lymphocyte function and NK cell activities in mice. Regardless of time and duration of EB-treatment, Arthus reaction and antibody response to SRBC were not modified by EB, but delayed hypersensitivity to SRBC was significantly enhanced only when EB was treated prior to SRBC-sensitization. EB slightly inhibited the proliferation responses of splenocytes to PHA-stimulation, but it significantly augmented the responses of these cells to S aureus Cowan 1 and Con A-activation, and these effects were manifested only when EB was added at culture initiation. EB did not influence Ig secretion of spleen cells but it significantly augmented the Con A-induced 1L 2 and MIF production of splenocytes. NK cell activities of splenocytes were markedly riled when effector cells were pretreated with EB and this augmentation was dine to the increase of binding affinity of effector cells to target cells and the target cell lytic activities of effector cells. These results led to the conclusion that EB triggers increase of cellular immune responses, such as delayed hypersensitivitiy, lymphokine production and NK cell activities. Also these results suggested that EB contains potent immune stimulants, which may provide the rational basis for their therapeutic use as one of the new biological response modifiers.

• Journal of Life Science
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• v.23 no.3
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• pp.448-461
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• 2013

Inflammatory bowel disease, known as Crohn's disease and ulcerative colitis, is an unexplained disease characterized by chronic inflammation that repeats a cycle of relapse, improvement, and complications. The cause of inflammatory bowel disease is not clearly known, but it is predicted that a complex of various factors precipitate its occurrence. In particular, inflammatory mediators, such as cytokine, induce an increase in cell-mediated inflammatory responses. Focal tissue damage then occurs in the intestinal mucosa because of the weakening of the immune-modulating functions of cotton. Immune and inflammatory responses do not decrease appropriately but continue until they lead to chronic inflammation. Current research has focused on the cytokine genes, which have important roles in these inflammatory responses. Cytokine is a glycoprotein that is produced mostly in activated immune cells. It connects the activation, multiplication, and differentiation between immune cells, which causes focal tissue damage and inflammatory response. Moreover, butyrate, which originates in dietary fiber and plays an important role in the structure and function of the intestinal area, shows control functions in the intestinal immune system by decreasing the proinflammatory cytokine and increasing the anti-inflammatory cytokine. Therefore, this research investigated the molecular mechanism of the anti-inflammatory effects of butyrate to comprehend the cytokine controlling abilities of butyrate in the immune cells. Butyrate is expected to have potential in new treatment strategies for inflammatory bowel disease.

• BMB Reports
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• v.32 no.5
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• pp.419-428
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• 1999

Tumor necrosis factor (TNF) receptor members have unique structures composed of 2-4 cysteine - rich pseudorepeats in the extracellular domain. On ligation by trimeric ligand molecules, oligomerization of three receptor molecules occurs, which in turn activates the receptor and recruits intracellular signaling molecules to the cytoplasmic tail to initiate biological events. Recently, the numbers of tumor necrosis factor receptor and ligand family members have been rapidly expanding. Functional characterization of the new members has indicated redundant roles with other known members as well as provided insights into novel functions. In particular, identification of soluble decoy receptors which have the ability to bind multiple ligands highlights a complex control mechanism of immune responses by these molecules. Studies of the new members have also revealed that the TNF receptor and ligand family members play an important role in other than the immune system.